Abstract 67: Blockade of VEGF-A signaling by Bevacizumab did not affect significantly in vivo metastatic dissemination of three colorectal cancer cells with different metastatic potential

Abstract

Abstract Colorectal cancer (CRC) is one of the deadliest cancers worldwide due to the high occurrence of metastasis in patients. Previous studies demonstrated that soluble factors modulates cancer-associated biological processes, including cell proliferation, angiogenesis and survival. Therefore, the dysregulation of secretory pathways is a crucial driver of CRC progression. This study aims to explore the influence of the microenvironment on the and the impact of the secretome on tumor biology. Initially, we implanted in immune-compromised NSG mice one representative CRC cell line (highly metastatic HCT-116, low metastatic HT-29 and non-metastatic 269) of a cluster analysis performed on cytokines profiles data of 20 CRC cells cultured in different in vitro conditions. Orthotopic and subcutaneous implantations of the cells were performed in two different set of experiments. Here, we found that the secretome pattern of the selected CRC lines was predictive of their tumor growth and metastatic dissemination in vivo. To determine if CRC standard care treatment might affect specific secretory pathways and in vivo metastasis, we orthotopically implanted again the three CRC cells (n=10 NSG mice for each cell line) and treated the mice with Bevacizumab (n=5) or with a control vehicle (n=5). Bevacizumab, was chosen due to the high expression of VEGF-A in the in vitro cytokine analysis and an upregulation in the serum of orthotopically implanted mice compared to the subcutaneous group. Serum was harvested before each treatment and at the termination time point. Tumor growth was followed by optical imaging and metastases were confirmed by terminal ex vivo imaging of the organs. As observed in the previous experiments, mice implanted with HCT-116 cells had the shortest latency and the highest intensity of tumor signal, compared to HT-29 and 269 lines, which belonged to the clusters of weakly and non-metastatic cells. The treatment with Bevacizumab did not influence the metastatic dissemination in the mice bearing HCT-116 and 269, whereas Bevacizumab-treated group implanted with HT-29 showed lower tumor signals compared to the control group, suggesting a sensitivity of these cells to Bevacizumab. Nevertheless, no statistically significant differences were observed in the ex vivo imaging analysis between Bevacizumab-treated and control groups in the different organs. A marked influence of Bevacizumab on tumor invasion in vivo was not determined. Future investigations could evaluate the co-injection of human monocytes and/or the administration of cross-reactive antibodies such as 2G11-2A05 to enhance the in vivo antitumoral activity of Bevacizumab. Furthermore, the human and mouse cytokine analysis of the organs and serum will help us to identify key players of the secretome to investigate their functional role in metastasis. Citation Format: Jacqueline Bersano, Dorothee Lenhard, Julia Schueler. Blockade of VEGF-A signaling by Bevacizumab did not affect significantly in vivo metastatic dissemination of three colorectal cancer cells with different metastatic potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 67.